20 Clinical Trials for Various Conditions
The research study is being conducted in health controls to better understand the effects of ketosis on brain functioning after 3 different, randomly assigned, 3-day dietary interventions and the acute effects of alcohol after consuming about 4-5 alcohol beverages. The labs visits will use magnetic resonance imaging (MRI) scans to study the brain, measuring levels of nicotinamide adenine dinucleotide (NAD), lactate, neurotransmitters glutamate, and Gamma-aminobutyric acid (GABA).
The goal of this pilot intervention is to learn about how a well-formulated ketogenic diet (WFKD) impacts various health factors in generally healthy adults. The main questions it aims to answer are: * Establish whether an 8-week isocaloric, WFKD improves body composition and metabolic biomarkers in adults without chronic disease. * Examine changes in transcriptomic sequencing pathways pre- and post-WFKD intervention. * Explore gut microbial changes in adults without chronic disease that consume a WFKD. Participants will follow a well-formulated ketogenic diet for 8-weeks. Study procedures include: * Weekly body weight tracking * Daily urinary ketone assessment * Pre/post stool samples for gut microbiota analyses * Pre/post DXA scans * Diet quality tracking through 3-day food records
Autophagy, which involves the degradation of aged or damaged cellular components, has been shown to extend healthspan and lifespan in multiple organisms, including flies, worms, and mice. Research has also demonstrated that autophagy declines with age in these simpler experimental models. However, human studies are lacking. Our study seeks to determine whether fasting, a robust stimulus of autophagy, upregulates autophagy in humans, and whether autophagy is reduced in healthy older people compared to healthy younger individuals.
The goal of this clinical trial is to test how specific components of diet affect brain function and behavior for individuals with bipolar. The main question it aims to answer is how glucose and ketones each affect the brain's response to risk and reward. Participants will be asked to provide blood (to assess baseline measures of how the body uses energy), and then to receive two MRI scan sessions, on separate days. During each MRI scan session, participants will play three games, from which they can win money, before and after drinking glucose (on one day) or ketones (on the other day). Investigators will compare individuals with and without bipolar to test whether the two groups differ in how their brains use energy, and to test how the brain's use of energy affects behavior.
Background: At least 30% of Americans have fatty liver disease. This means that they store too much fat in the liver. At the moment lifestyle changes are the only way to treat this problem. Objective: To test how (1) a low-carbohydrate diet and (2) a supplement called nicotinamide riboside (NR) affect how a person s body uses dietary fat. Eligibility: Men aged 18 to 65 and women aged 18 to 50 who are healthy volunteers with a body mass index (height to weight ratio) of 25 or more. Adults with maturity-onset diabetes of the young type 2 (MODY2) are also needed. Design: Participants with diabetes will have 1 screening visit and a 9-day clinic stay. Healthy volunteers will have 1 screening visit and 2 clinic stays of 1 to 2 weeks each. During screening, all participants will have a physical exam with blood and urine tests. They will have their heart rhythm measured while riding a gym bike. NR is a pill taken by mouth. Only healthy volunteers will take the NR, for 14 days at a time, during 1 clinic stay. During their other stay, they will take placebos; these are pills that look like the study supplement but contain no NR. During each clinic stay, all participants will eat a normal American diet. Then they will eat a ketogenic "low-carb" diet for 5 days. Participants will have many tests, including: Sleeping every night and having two 24-hour stays in a special room that measures the gases their body uses and produces. Drinking a high-fat shake, then remaining seated for 5 hours while their blood and breath are monitored. Having a substance injected into the arm and remaining seated for 3 hours while their blood is measured. Wearing monitors to measure their activity levels. Another monitor will measure their blood glucose levels. Having imaging scans. ...
Original research article entitled Induced and Controlled Dietary Ketosis as a Regulator of Obesity and Metabolic Syndrome by Madeline Gibas for consideration for publication in a clinical journal. This research manuscript builds on previous landmark studies that report that major weight and fat mass loss in type II (T2D) patients who were fed a very low carbohydrate, ketogenic diet. In this manuscript, the investigators outline our research study that showed statistically significant (p \< 0.05) changes over time in hemoglobin A1c, weight, BMI, body fat percentage and ketones for patients with metabolic syndrome who were fed a very low carbohydrate diet, ketogenic diet.
The goal of this clinical research study is to test what effects a ketone drink will have in people with heart failure with preserved ejection fraction (HFpEF), including on exercise and heart function. Patients with HFpEF often have difficulty exercising, and our goal is to understand whether a ketone drink changes much patients can exercise. The study has three visits, including a baseline visit to assess for study eligibility, and two visits (one after 8 weeks of a ketone drink or a placebo drink, and another one after 8 weeks of whichever drink the participant did not receive the first time).
The research study is being conducted to better understand the effects of ketones and alcohol on brain functioning and brain metabolism. Participants will be asked to undergo three identical MRI visits after three single-dose interventions: (1) drink a ketone supplement drink, (2) drink an alcoholic beverage, (3) no intervention. These interventions will be randomly assigned (meaning everyone receives all 3 interventions, but in different orders).
The goal of this clinical trial is to learn the effects of ketone supplement compared to placebo on alcohol withdrawal symptoms during a 4 day alcohol withdrawal management treatment in adults with moderate to severe alcohol use disorder at the Hospital of the University of Pennsylvania, Cedar Detox Center.
This outcome of this study will elucidate how the phenotype of the individual modulates the KE metabolic effect. Most studies of KE have been in homogenous populations, usually young, male athletes. However, two striking experiments using identical, body weight adjusted KE doses in healthy and obese individuals found that BHB area under the curve (AUC) and removal was reduced by obesity and poor metabolic health. Similarly, ketone infusion experiments found that diabetes, obesity, and insulin resistance alter BHB metabolism. It is important to determine how obesity affects KE 'sensitivity' (i.e., breakdown and oxidation) because the increasing prevalence of obesity as a function of age. Age may be another important source of variation in ketone metabolism. The genes that control the ketone system are regulated by a cascade of transcription factors and hormones including PPARα and FGF21, which are themselves known to be affected by aging and dietary status, and the cellular protein sensor target of rapamycin (TOR). Aberrant hyperactivation of TOR with aging may reduce ketogenesis, while it was observed that a long-term ketogenic diet specifically up-regulated PPARα activity. Preliminary work revealed substantial changes across mouse lifespan in the expression of ketone-related genes in the liver such as Hmgcs2 (rate limiting for ketone production) and Bdh1 (rate limiting for BHB oxidation) between young, middle-aged, and old mice, with a nadir of gene expression in middle age before increasing again late in life. Substantial age differences were found in response to matched doses of oral KE in mice and in rats. These data may have important implications for treating people of different ages and for translating KE technologies into the Department of VA. Therefore, this project plans to study individual responses to KE ingestion across the lifespan, against the background of varying metabolic health
Small exploratory open-label pilot study to assess supplementation of a ketone ester (KetoneAid) as a potential therapy for persons with Parkinson disease (PD), Parkinson Disease Dementia/Lewy Body Dementia (PDD/LBD), and healthy controls.
The purpose of this study is to help us better understand how plasma ketones respond to a low-carb diet when combined with an SGLT2 inhibitor.
The scientific goal of this study is to examine the effects of a ketogenic diet on hypoglycemia tolerance and brain function in people with type 1 diabetes mellitus (T1D) and to clarify the mechanistic role of ketones in this process. Glycemic management of T1D is typified by alternating periods of hyper- and hypo-glycemia. Because brain metabolism under usual conditions depends on glucose, acute hypoglycemia leads to immediate complications including impaired cognitive function and a counter-regulatory hormone response. Recurrent hypoglycemia is associated with functional and structural changes in the brain and contributes to the cognitive decline observed in individuals with diabetes. The state of nutritional ketosis (as it occurs during fasting or when following a ketogenic \[very low carbohydrate\] diet) may protect against these acute and chronic complications. As the body relies on fat metabolism, ketone bodies build up and provide an alternative fuel for the brain. Studies during hypoglycemia have shown better cognitive function and less hypoglycemia symptoms in the setting of nutritional ketosis or with ketone administration. This physiological benefit may have special relevance for people with T1D who experience hypoglycemia frequently. To date, no mechanistic studies have examined brain effects of nutritional ketosis in T1D; nor have any trials explored the potential relevance of this for diabetes care.
The study explores whether selective memory complaints (SMC), mild cognitive impairment (MCI) and the comorbidity of Metabolic Syndrome symptomatic of peripheral and cerebral hypo-metabolism with corresponding epigenetic shifts in global DNA (deoxyribonucleic acid) methylation (away from nutrient availability and toward biosynthesis) are initiated by chronic metabolic inflexibility, over-activation of the mTOR (mammalian target of rapamycin) pathway, and the deregulation of neural oxidative phosphorylation.
The objective of this randomized crossover study is to examine the influence of consuming a ketone ester plus carbohydrate (KE+CHO) supplement on substrate oxidation and physical performance in 15 healthy adults. Following a 48-hr muscle glycogen normalization period, volunteers will consume either an isocaloric KE+CHO (KE: 573 mg KE/kg body mass, CHO: 110 g) or isocaloric CHO drink and complete 90-min of metabolically-matched, load carriage (\~30% body mass) steady-state aerobic (\~60 ± 5 % of VO2peak) exercise on a treadmill. Glucose tracers will be used to assess glucose turnover, and contribution to exogenous and plasma glucose oxidation. Serial blood draws will be collected during each trial to assess endocrine and circulating substrate responses. After steady-state exercise volunteers will complete a time to exhaustion (TTE) physical performance tests at 85% VO2peak on a treadmill. Volunteers will then be provided with food for the remainder of the day. Following a 10-hr overnight fast, volunteers will return to the laboratory and consume the same supplement (KE+CHO or CHO) as they did the previous day. Volunteers will then perform a 4-mile load carriage time trial on a treadmill. Following a minimum 7-day washout period, volunteers will return to the laboratory to complete the second arm of the study. The primary risks associated with this study include those associated with exercise, blood draws, and gastrointestinal discomfort from the KE+CHO supplement.
The goal of this randomized clinical trial is to be adequately powered to evaluate the effect of ketogenic metabolic therapy on the quality of life in serious mental illness, schizophrenia, bipolar disorder, major depressive disorder.
The purpose of this study is to understand the effects of a ketone drink on exercise capacity and other cardiovascular parameters in patients with heart failure. In heart failure, patients are limited in their ability to do all the things they want to do, and exercise as much as they would like, due to becoming tired and short of breath early. There may be several reasons why these symptoms occur. This study is assessing whether the ketone drink can improve these symptoms. This drink has been given status by Food and Drug Administration as "generally regarded as safe". The use of DeltaG in this study is experimental. DeltaG has not been approved by the Food and Drug Administration (FDA) for the use being evaluated in this study.
Despite major technological advances, management of type one diabetes mellitus (T1D) remains suboptimal, putting millions of people at risk for immediate and long-term complications. After meals, a mismatch between carbohydrate absorption rate and insulin action typically leads to alternating periods of hyper- and hypoglycemia. A conceptually promising approach to control both problems is dietary carbohydrate restriction to reduce postprandial blood glucose changes and insulin needs. In a prior survey study, the investigators documented exceptional glycemic control (HbA1c 5.67%) and low acute complication rates among 316 children and adults with T1D consuming a very-low-carbohydrate diet. To test the feasibility of this approach, the investigators will conduct a randomized-controlled feeding study involving 32 adults and adolescents with T1D. Participants will be randomized to receive a very low carbohydrate vs. standard carbohydrate diet. Participants will be in the study for 12 weeks and receive all their meals by meal delivery.They will share continuous glucose monitoring data with the study team and be in close communication to adjust insulin doses as needed. All participants will have a screening visit, an individual or group education session, and 3 study visits to evaluate diabetes control and metabolic health. Some of these visits will have a fasting blood draw. Two of the visits will also comprise additional metabolic studies to assess glucagon response and brain function during hypoglycemia by magnetic resonance imaging (MRI). Participants will have IV catheters placed and receive IV insulin to drop blood glucose levels to 50 mg/dl for up to 30 minutes. The primary outcome will be HbA1c change from baseline. Secondary outcomes include detailed measures of glycemic variability, metabolic health, and quality of life.
Exogenous ketone supplements in the form of beta-hydroxybutyrate can be utilized as an alternate energy source (in place of glucose) for all cells except red blood cells. Exogenous ketone administration has been shown to be beneficial in terms of reducing oxidative stress, improving neuronal energy supplies, and maintaining normal blood glucose levels. The purpose of this study is to determine the effects and safety of supplementing with exogenous ketones for 6-weeks in healthy college-aged males and females. The results of this proposed study will determine whether exogenous ketone supplementation can be useful in promoting better body composition, energy levels, and blood cholesterol, glucose, and insulin levels.
This research study is being performed to begin to determine the effectiveness of two dominant bariatric surgery procedures versus an intensive lifestyle intervention to induce weight loss in patients and promote improvements in Type 2 diabetes mellitus (T2DM) in moderately obese patients. T2DM is currently the 6th leading cause of mortality in the United States and is a major cause of kidney failure, blindness, amputations, heart attack, and other vascular and gastro-intestinal dysfunctions. Traditionally, treatments include intensive lifestyle modifications with or without glucose lowering agents. Neither treatment alone, or in combination, results in complete resolution of diabetes and its potential long-term complications. Bariatric surgery has been proven as an effective treatment to accomplish sustained and significant weight loss for those with severe obesity and has been shown to induce long-term remission of T2DM. However, despite enthusiasm for these potential treatment options, it is not clear whether diabetes is influenced by the type of surgery or by the amount of weight lost or if bariatric surgery is more effective than non-surgical weight loss induced by diet and physical activity in T2DM patients with moderate BMIs (30-40kg/m2; Class I and Class II obesity, or approximately 65-95 pounds overweight depending on your height). More well-controlled studies are needed to more completely inform health care decision making and clinical practice in this area. This research study aims to obtain preliminary information regarding the effectiveness of two major types of bariatric surgery, Laparoscopic Roux-en-Y Gastric Bypass and Laparoscopic Adjustable Gastric Banding versus an intensive lifestyle intervention to induce weight loss with diet and increased physical activity.